Were “Dry” Powder Asthma and COPD Inhalers a Big OOPS?

For decades, people with asthma and COPD (chronic obstructive pulmonary disease) relied upon “metered-dose inhalers” to help them breathe. These “puffers,” as they are called in Australia, Canada and the UK, deliver a liquid spray to the airways. Most contained a corticosteroid to calm inflammation in the lungs along with a long-acting bronchodilator to dilate constricted air passages. Did the switch from metered-dose inhalers to dry-powder inhalers create an unexpected problem? A new study in JAMA Internal Medicine (July 7, 2025) suggests it might have.

Phasing Out CFCs for HFAs and Dry-Powder Inhalers:

The Food and Drug Administration became concerned about the propellant gas used in asthma and COPD inhalers during the late 20^th century. That’s because chlorofluorocarbon (CFC) inhalers were thought to deplete the ozone layer in the atmosphere. The US Clean Air Act prohibited the use of “nonessential” ozone-depleting substances.”

The FDA announced that it would “ban CFC albuterol inhalers by December 31, 2008 (JAMA Internal Medicine, July 1, 2015). They were to be replaced by hydrofluoroalkane (HFA) inhalers, which were considered less likely to deplete the ozone layer. HFAs are still a gas propellant, but they are considered environmentally friendlier than CFC gas propellants.

Dry-Powder Inhalers (DPIs):

Dry-powder inhalers need no propellant. Instead, they rely upon the patient to suck the active drug powder directly into the lungs.

The theory was that eliminating the gas propellant would be good for the environment and easier for patients to use. Drug companies may have liked the idea that DPIs would likely be more stable than liquid drugs using propellants.

Are Dry-Powder Inhalers Better Than Metered-Dose Inhalers?

This may seem like an inside-baseball kind of question, but it is really crucial for prescribers and patients. I suspect that both the drug companies and the FDA assumed that the delivery systems were less important than the actual medicines. The new study in JAMA Internal Medicine (July 7, 2025) suggests otherwise.

The researchers are from the Ann Arbor Veterans Affairs and my alma mater, the University of Michigan. They tracked an intriguing “natural” experiment within the Veterans Health Administration (VHA). This organization opted to change its asthma/COPD inhalers as a result of a “competitive bidding process.”

Instead of the metered-dose inhalers containing a combination of budesonide-formoterol (Symbicort), the VHA opted for a dry-powder branded generic combination of fluticasone-salmeterol (Wixela Inhub, similar to the brand name Advair Diskus).

Here is how the authors of the research describe the switch from a metered-dose inhaler to a dry-powder inhaler:

“The VHA formulary change created a natural experiment to evaluate the clinical difference in outcomes associated with switching both medication (budesonide-formoterol vs fluticasone-salmeterol) and delivery device (metered-dose inhaler vs dry-powder inhaler) in a nationwide cohort of veterans. We hypothesized that clinical outcomes would be similar between budesonide-formoterol metered-dose and fluticasone-salmeterol dry-powder inhaler therapy, and that clinical equivalence could provide compelling evidence to support broader adoption of the less expensive and environmentally sustainable dry-powder alternative. To test this hypothesis, we conducted a primary within-person analysis and a secondary matched cohort analysis to assess the association between the formulary change and clinical outcomes.”

And the Envelope Please!

If you are still with me on this fascinating natural experiment, you realize that the Veterans Health Administration was trying to save money by changing its formulary from Symbicort to a branded generic formulation of Advair Diskus. In doing so, the VA was going from a metered-dose inhaler to a dry-powder inhaler. The assumption was that it would be a win-win outcome: save money and save the environment. Over 250,000 VA patients had their puffers switched.

I suspect that the authors were surprised by the outcome, though they don’t come out and say that.

The Outcomes of the Inhaler Study:

“Findings In this primary self-controlled case series and secondary matched cohort study of 260 268 and 258 577 US veterans, respectively, transition to fluticasone-salmeterol dry-powder inhaler therapy under a national formulary change was associated with higher rates of prednisone use and increased all-cause and respiratory-related emergency department visits and hospitalizations.

“Meaning These results suggest that there was an increase in adverse health outcomes after the shift from budesonide-formoterol metered-dose inhaler therapy to fluticasone-salmeterol dry-powder inhaler therapy in the Veterans Health Administration.”

What Will Pulmonologists Make of These Inhaler Study Results?

This may not seem like a big deal, but I believe it might be an earthquake in the pulmonary community. The idea that the dry-powder inhaler was associated with greater need for oral prednisone was not welcome news. And higher “health care utilization” suggests that patients were not doing as well as they had previously when relying on metered-dose inhalers.

The authors raise a critical issue:

“A key question raised by our study is whether the increased incidence of adverse outcomes among patients who switched to the dry-powder fluticasone-salmeterol inhaler was associated with the medication, the device, or other factors. The answer likely involves all 3 factors.”

First, they point out that while the ingredients in both puffers are similar in pharmacological action, the corticosteroid fluticasone:

“is associated with a higher pneumonia risk than budesonide, likely due to its more sustained systemic and local immunosuppressive effects.”

I wonder how many physicians are aware of that possibility. Fluticasone is a very popular corticosteroid in both asthma and COPD inhalers as well as in some OTC nasal allergy medicines.

They continue:

“Second, differences in drug delivery mechanisms may have influenced outcomes.”

“Third, the formulary change may have disrupted established treatment routines, with evidence suggesting that forced device switching can decrease medication adherence, lead to errors in inhalation technique, and worsen clinical outcomes.”

The Bottom Line…Literally:

The researchers conclude their important investigation this way:

“Our results highlight the tension between reducing inhaler costs, improving clinical outcomes, and addressing the environmental impact of care delivery. While the formulary change likely lowered inhaler expenditures and reduced direct inhaler-related greenhouse gas emissions—the equivalent of taking approximately 6000 gasoline-powered passenger vehicles off the road for 1 year—higher health care utilization could offset these climate benefits by increasing resource-intensive ED [emergency department] visits and hospitalizations. For health systems aiming to align with decarbonization goals, interventions must optimize clinical outcomes and net greenhouse gas emissions while balancing costs.”

Final Words:

I apologize for this rather long and complicated report about asthma/COPD inhalers. It was very technical, I admit. But I think this research is very important. There are millions of people with both asthma and COPD and this research could impact their treatment program.

No one should ever stop or change their inhaler without close collaboration with the person in charge of treatment. But there is a good chance that your busy doctor may not see this research right away. That is why you may wish to send a link or a paper copy of the study in JAMA Internal Medicine, July 7, 2025. It is certainly worth a conversation with your prescriber.

A small favor, please. If you know someone who might appreciate this new research, please send it along via email or social media. Just scroll to the top of the page and click on the appropriate icons. While you are at it, why not encourage friends and family to sign up for our free newsletter at this link? That way they too can have access to the latest research on a variety of health topics. Thank you for your support.